DESCRIPTION, OVERALL (provided by applicant): The University of Southern California Research Center for Liver Diseases, funded since 1995, has the goal of fostering and facilitating interdisciplinary research in liver and digestive disease. The Center has 41 members and 22 affiliated members. The Biomedical Research Base consists of four major Themes supported by 58 peer-reviewed grants totaling $10.1 million in annual direct costs. These Themes include: a) viral hepatitis, hepatocellular and colon cancer: b) liver injury: c) cell biology, signal transduction and transport: d) regulatory biology: liver metabolism, gene expression, and liver/intestinal growth and development. Four core facilities support this Research Base: 1) Administrative Core which oversees the operations and budget of the Center including the Cores, P/F program and enrichment program, 2) Cell Culture Core, which provides isolated and primary cultured rat, mouse and human hepatocytes and various cell lines;3) Cell and Tissue Imaging Core, which consists of two subcores: Microscopy Subcore, which provides confocal and fluorescence microscopy using various platforms, and Histology Subcore, which provides liver tissue slide preparation, routine and special staining, and interpretation. 3) Analytical, Metabolic, Instrumentation Core, which consists of a base Core and two subcores;the base core provides oversight of the subcores and access to a wide range of equipment shared by Center members and specialized HPLC analyses;the Small Molecule Subcore (metabolic component) provides quantitation of analytes using mass spectrometry, and the Proteomic Subcore uses state-of-the-art mass spectrometry approaches for protein identification. The Center supports Pilot Feasibility projects in diverse areas related to the themes of the Research Base. Current projects include studies of: a) farnesoid X receptor, bile acids and liver regeneration;b) the role of Myc-max and Mnt-max in regulation of p53 and cyclin D1 by toxic bile acid;c) salvage of short bowel syndrome by tissue engineered intestine;d) development of a model for engraftment of human embryonic stem cell-derived hepatocytes to regenerate liver;and e) elucidation of the role of AP-1 and DNA damage repair in HCV-induced hepatocelluar carcinoma.